Hormone-Resistant Prostate Cancer, Metastatic Prostate Carcinoma, Recurrent Prostate Carcinoma, Stage IV Prostate Cancer
Conditions
Brief summary
In this study, patients who have metastatic prostate cancer that does not respond to hormone treatment and who have mutations in certain cancer-related genes will be treated with docetaxel and carboplatin chemotherapy.
Detailed description
This is a phase 2 study of the combination of docetaxel and carboplatin in patients with germline inactivation of genes in the homologous recombination pathway, including BRCA1, BRCA2, and Ataxia Telangiectasia Mutated (ATM). PRIMARY OBJECTIVE To assess rate of 50% Prostate Specific Androgen (PSA) decline to docetaxel and carboplatin
Interventions
DRUGCarboplatin
Chemotherapy
DRUGDocetaxel
Chemotherapy
Sponsors
Prostate Cancer Foundation
VA Puget Sound Health Care System
Seattle Institute for Biomedical and Clinical Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients meeting the following inclusion criteria will be eligible to participate in this study: 1. Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information. 2. Age \> 18 years 3. Known prostate cancer 4. Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy. Patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy. 5. Castration resistant prostate cancer as defined by serum testosterone \< 50ng/ml and one of the following: * PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart. * Evaluable disease progression by modified RECIST (Response Evaluation Criteria in Solid Tumors). * Progression of metastatic bone disease on bone scan with \> 2 new lesions. 6. Prior therapy with abiraterone acetate, enzalutamide, or docetaxel. There is no limit to the number of prior treatment regimens. 7. Presence of metastatic disease on scans. 8. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2. 9. Life expectancy \>12 weeks. 10. No prior malignancy is allowed except: * Adequately treated basal cell or squamous cell skin cancer or * In situ carcinoma of any site or * Other adequately treated malignancy for which the patient has been disease-free for at least one year (any prior chemotherapy is allowed). 11. Patients must have adequate organ and marrow function as defined below obtained within 14 days prior to start of therapy: 1. Absolute neutrophil count \>1.5 x 109 cells/L 2. Hgb \> 9.0 g/dL 3. Platelets \>100,000 x 109/L 4. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels \< 1.5 x Upper Limit of Normal (ULN) 12. Presence of germline inactivation of BRCA1, BRCA2, ATM OR one of the following: * Patients with clearly deleterious germline mutations of other genes involved in homologous DNA repair may be included at the investigator's discretion. * Patients with homozygous inactivation of genes involved in homologous recombination from primary or metastatic tumor as assessed by a Clinical Laboratory Improvement Amendments (CLIA) level assay for DNA sequencing may be included. * Patients with a signature of homologous recombination deficiency in primary or metastatic tissue may be included (VA Puget Sound only).
Exclusion criteria
Patients who meet any of the following criteria will be excluded from the study: 1. Currently receiving active therapy for other neoplastic disorders. 2. Histologic evidence of small cell carcinoma (morphology alone - immunohistochemical evidence of neuroendocrine differentiation without morphologic evidence is not exclusionary). 3. Prior treatment with platinum-based chemotherapy for prostate cancer. 4. Known parenchymal brain metastasis. 5. Active or symptomatic viral hepatitis or chronic liver disease. 6. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of \< 35 % at baseline, if done. 7. Treatment with an investigational therapeutic within 30 days of Cycle 1. 8. Patients with dementia/psychiatric illness/social situations limiting compliance with study requirements or understanding and/or giving of informed consent are not eligible 9. Any medical conditions, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained are not eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Achieving >= 50% Reduction in PSA According to Prostate Cancer Working Group 3 (PCWG3) Criteria | From Day 1 of treatment and up to 30 days after completion of treatment (typically up to 10 cycles of chemotherapy) | Achievement of a PSA50 decline is whether the treatment results in a 50% or greater decline in PSA from baseline PSA prior to therapy |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Docetaxel, Carboplatin) Docetaxel 60 mg/m2 will be administered on Day 1 of each 21-day cycle. Carboplatin Area Under the Curve (AUC) 5 will be administered on Day 1 of each 21-day cycle.
Docetaxel and carboplatin should be administered per institutional guidelines. Treatment will be repeated until disease progression or unacceptable toxicity.
Carboplatin: Chemotherapy
Docetaxel: Chemotherapy | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Inability to comply with study procedures | 1 |
Baseline characteristics
| Characteristic | Treatment (Docetaxel, Carboplatin) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Patients with metastatic resistant prostate cancer | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Percentage of Patients Achieving >= 50% Reduction in PSA According to Prostate Cancer Working Group 3 (PCWG3) Criteria
Achievement of a PSA50 decline is whether the treatment results in a 50% or greater decline in PSA from baseline PSA prior to therapy
Time frame: From Day 1 of treatment and up to 30 days after completion of treatment (typically up to 10 cycles of chemotherapy)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Docetaxel, Carboplatin) | Percentage of Patients Achieving >= 50% Reduction in PSA According to Prostate Cancer Working Group 3 (PCWG3) Criteria | 2 Participants |